Regulation of Interneuron Function in the C. elegans Thermoregulatory Pathway by the ttx-3 LIM Homeobox Gene

Abstract

Neural pathways, which couple temperature-sensing neurons to motor and autonomic outputs, allow animals to navigate away from and adjust metabolism rates in response to the temperature extremes often encountered. ttx-3 is required for the specification of the AIY interneuron in the C. elegans neural pathway that mediates thermoregulation. ttx-3 null mutant animals exhibit the same thermotactic behavioral defect as that seen with laser ablation of AIY in wild type, suggesting that AIY does not signal in this mutant. ttx-3 encodes a LIM homeodomain protein. A ttx-3-GFP fusion gene is expressed specifically in the adult AIY interneuron pair, which connects to thermosensory neurons. In ttx-3 mutant animals, the AIY interneuron is generated but exhibits patterns of abnormal axonal outgrowth. Thus, the TTX-3 LIM homeodomain protein is likely to regulate the expression of target genes required late in AIY differentiation for the function of this interneuron in the thermoregulatory pathway. The ttx-3-dependent thermosensory pathway also couples to the temperature-modulated dauer neuroendocrine signaling pathway, showing that ttx-3 specifies AIY thermosensory information processing of both motor and autonomic outputs.

Behavioral plasticity in C. elegans: Paradigms, circuits, genes

“…It means that we can expect to correlate gene activity with individual cells within a circuit and thus reduce the complexity of analysis of a mutant phenotype. For example, the odr-7, ttx-1, and ttx-3 genes each affect the development of a single type of neuron in specific neural circuits (Sengupta et al, 1994;Hobert et al, 1997;Satterlee et al, 2001); if the respective gene had been expressed in several neurons of the circuit, the interpretation of the mutant phenotype would have been much more complex.…”

Temperature sensing across species

“…As the behavioral phenotype of ttx-1 mutants is synonymous with that observed in AFD-ablated animals, a similar correlation has been made with ttx-3 mutants and animals in which the interneuron AIY is killed [5,16]. Like ttx-1, the genetic basis for ttx-3 mutants appears to involve disrupted gene expression as ttx-3 encodes a LIM homeodomain protein, a class of highly conserved neural regulatory genes [16,17].…”

“…Like ttx-1, the genetic basis for ttx-3 mutants appears to involve disrupted gene expression as ttx-3 encodes a LIM homeodomain protein, a class of highly conserved neural regulatory genes [16,17]. Consistent with the behavioral phenotype, Ttx-3 is expressed exclusively in adult AIY interneurons and is likely involved in regulating expression of genes required for AIY differentiation as excessive neurite outgrowth is observed in axonal projections.…”

Modulation of the assay system for the sensory integration of 2 sensory stimuli that inhibit each other in nematode Caenorhabditis elegans

“…[kyIs37 [odr-10::GFP]] (a marker that labels AWA sensory neurons) [30] , HA3 [nuIs11 [osm-10::GFP]] (a marker that labels ASH sensory neurons) [31] , OH3701 [otIs173 [ttx-3::GFP]] (a marker that labels AIY interneurons) [32] , VM182 [akEx51 [glr-2::GFP]] (a marker that labels AIA interneurons) [33] , and BC12233 [sEx12233[C13G5.1::GFP]] (a marker that labels AIZ interneurons) [34] . All the single mutants used in the present study had a loss-of-function mutation.…”